Compositions and method for hair loss prevention

ABSTRACT

A formulation for hair loss prevention comprising at least one hair loss preventive ingredient known to inhibit the hormonal mechanism underlying androgenetic hair loss and a mixture of water and at least one aprotic organic solvent capable of solubilizing sebum and allowing the hair loss preventive ingredient to reach the skin and/or hair follicle, and methods of using the same.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. provisional application Ser.No. 60/854,810, filed Oct. 27, 2006, hereby incorporated by reference.

FIELD OF THE INVENTION

The invention pertains to the field of hair loss prevention using aformulation endowed with the ability to reach the papilla and deliver adrug that will encourage hair growth, therefore resulting in preventionand arrest of male pattern baldness (androgenetic alopecia) in humansubjects; and a method for the application of the formulation in orderto achieve scalp degreasing, dandruff removal or hair loss prevention.

BACKGROUND OF THE INVENTION

Androgenetic alopecia (AGA) is a genetically based disorder of thescalp, which results in gradual and permanent miniaturization of thehair follicles on regions of the scalp ultimately resulting in baldness.This condition, while not life threatening, is psychologically highlydevastating in affected people and can result in depression and poorquality of life.

Research has shown that the phenomenon is connected to the male hormonetestosterone. Kaufman, K D, “Androgens and alopecia,” Mol. Cell.Endocrinol., 198(1-2), 89-95 (2002). Women and men with low levels oftestosterone are less susceptible to AGA. Yet testosterone by itself isnot sufficient to trigger the process. The process requires anadditional step of chemical transformation in order to be effective.This additional process was shown to be the testosterone reduction todihydrotestosterone (DHT), the ultimate baldness effector. Choi et al.,“Biochemical roles of testosterone and epitestosterone to 5alpha-reductase as indicators of male-pattern baldness,” J. Invest.Dermatol., 116(1), 57-61 (2001).

The conversion occurs in the body by means of the enzyme 5α-reductase,which is abundant in the skin and follicles of susceptible individuals.It is this same hormone that stimulates sebaceous glands, located inhair follicles, to produce sebum which is then secreted onto the skin.An excessive sebum production is known as seborrhoea and is oftenassociated with AGA. Mercurio et al., “Androgen physiology and thecutaneous pilosebaceous unit,” J. Gend. Specif. Med., 3(4), 59-64(2000). Seborrhoea exacerbates the effects of balding because it causesstickiness of hair and favours the production of dandruff.

Dandruff itself (Pityriasis capitis) is another relevant problem forbalding individuals and a potential source of stress and socialembarrassment. It is due to an excessive turnover of scalp skin which inturn results in copious shedding of whitish flakes. The cause ofdandruff has been identified in the fungus Malassezia globosa whichmetabolises scalp triglycerides (sebum) into oleic acid which is anirritant and provokes the turnover increase. Therefore, the threeproblems mentioned are all connected and tend to afflict overlappinggroups of individuals.

Many compounds to date have been shown to inhibit DHT formation fromtestosterone, such as finasteride, dutasteride, zinc, and azelaic acid.See, Stamatiadis, et al. “Inhibition of 5 alpha-reductase activity inhuman skin by zinc and azelaic acid,” Br. J. Dermatol. 119(5), 627-32(1988); Olszewska et al., “Effective treatment of female androgenicalopecia with dutasteride,” J. Drugs Dermatol., 4(5), 637-40 (2005); andLeyden et al., “Finasteride in the treatment of men with frontal malepattern hair loss,” J. Am. Acad. Dermatol., 40(6 Pt 1), 930-7 (1999). Ofthese, finasteride has been licensed for commercial use for the purposeof preventing AGA.

Many other compounds have been shown to stimulate hair growth by yetunclear mechanisms which may be connected to increased blood supply tothe follicle and stimulated cell proliferation. These include minoxidiland tretinoin. See, Karam P., “Topical minoxidil therapy for androgenicalopecia in the Middle East. The Middle-Eastern Topical Minoxidil StudyGroup,” Int. J. Dermatol., 32(10), 763-6 (1993); and Bazzano et al.,“Topical tretinoin for hair growth promotion,” J. Am. Acad. Dermatol.,15(4 Pt 2), 880-883 and 890-893 (1986). Minoxidil has been licensed forcommercial use for the treatment of AGA.

The saw palmetto extract is a common herbal supplement taken orally andknown to be beneficial in enlarged prostate patients. Medical researchhas shown that it is a good inhibitor of 5α-reductase, the enzymeresponsible for generating DHT, the harmful form of testosterone. See,Habib, F. K., et al. “Serenoa repens (Permixon) inhibits the 5alpha-reductase activity of human prostate cancer cell lines withoutinterfering with PSA expression”, Int. J. Cancer 114 (2), 190-4 (2005).It is widely available, taken systemically, and has a good safetyrecord. The only common remedy for sebum overproduction is detergency.To this date, there are no topical formulas with a proven capacity toreduce sebum production, therefore, the only option is sebum removalonce produced. There are many detergents available, but they all comewith the drawback that a rinse is required to flush them and so accessto water and hair drying equipment is necessary. For dandruff preventionfighting the responsible fungus will dramatically alleviate thecondition. Many antifungal compounds are used cosmetically as additivesto shampoos, including zinc pyrithione, tar, selenium sulfide, andketoconazole. These compounds all have a long usage history which hasproven they are effective and safe to use.

The prior art relates to treatment of the hair strands themselves (suchas thickening) and not skin penetration. Moreover, there is no intent todeliver active ingredients to hair follicles or to treat sebum. Thepresent invention is directed to addressing the need for compositionsthat remove excess sebum and dandruff while also stimulating hairgrowth.

SUMMARY OF THE INVENTION

One embodiment of the invention encompasses formulations for hair lossprevention comprising an aprotic organic solvent/water mixture and atleast one hair loss preventive ingredient known to inhibit the hormonalmechanism underlying androgenetic hair loss. The aprotic organic solventmay be an ester, aldehyde, or ketone. Typically, the aprotic organicsolvent may have C₂-C₁₀ atoms. The aprotic organic solvent may bepresent in an amount of 60% to 90% by weight of the formulation. Thewater may be present in an amount of 2% to 20% by weight of theformulation.

The hair loss preventive ingredient may be a C₆-C₁₄ dicarboxylic acid,finasteride, minoxidil, tretinoin, or a herbal extract. Preferably, theC₆-C₁₄ dicarboxylic acid is azelaic acid. When the hair loss preventiveingredient is azelaic acid, it is present in an amount of about 2% to30% by weight of the formulation and preferably between 10% and 25% byweight. Preferably, the herbal extract is saw palmetto extract. When thehair loss preventive ingredient is saw palmetto extract, it is presentin an amount of about 0.5% to 5% by weight of the formulation. When thehair loss preventive ingredient is finasteride, minoxidil, or tretinoin,it is present in an amount of about 0.001% to 5% by weight of theformulation. The composition may further comprise at least oneantifungal compound. Preferably, the antifungal compound include zincpyrithione, tar, selenium sulfide, ketoconazole, or tea tree oil. Whenthe antifungal compound is zinc pyrithione, it is present in an amountof about 0.001% to 5% by weight of the formulation.

Another embodiment of the invention encompasses a method to prevent hairloss and degrease the scalp comprising applying a hair loss preventionformulation in a therapeutically sufficient amount to an area of skinand massaging the area of skin until the formulation is absorbed throughthe skin, wherein hair loss prevention formulation has an aproticorganic solvent/water mixture and at least one hair loss preventiveingredient known to inhibit the hormonal mechanism underlyingandrogenetic hair loss.

DETAILED DESCRIPTION OF THE INVENTION

The invention is directed to formulations that address both the problemof seborrhoea and of AGA. Thus, the invention relates to the cosmeticfield of hair loss prevention, dandruff removal, and/or scalp cleansing.Not to be limited by theory, however, it is believed that the solventmixture of the composition, which has the same lipophilicity as thescalp itself, interacts with the scalp in such a manner as to dissolvethe sebum layer which covers the scalp in individuals affected byexcessive sebum production (greasy skin) and allows for the efficientpenetration of the active ingredients into the skin and/or hairfollicles. It is these active ingredients in the formulation, which areknown in the literature to interfere with the hormonal mechanismsunderlying androgenetic alopecia (male hair loss), that prevent hairloss. In addition, the formulation ensures that dandruff production isslowed to normal levels.

Thus, the formulation for the prevention of hair loss comprises asolvent/water mixture and at least one hair loss preventive ingredient,wherein the solvent/water mixture is capable of solubilizing sebum andallowing the hair loss preventive ingredient to reach the skin and/orhair follicle. The formulations may be in the form of a gel, paste,cream, lotion, or ointment, or on a carrier (e.g. on sponges, indispensers or cotton applicators).

The solvent/water mixture is a mixture of water and at least one solventthat can solubilize sebum (grease). The purpose of sebum is to providethe skin with a waterproof barrier to prevent microbial invasion,however, sebum itself is a combination of fatty acids and esters whichare quite insoluble in water and usually require the use of surfactants(i.e., shampoo) for removal. The solvent should effectively dissolve thesebum layer and temporarily create a permeability breach in the skin (orupper epidermis). An advantage of the composition over existing ones isits unique lipophilicity which allows its active ingredients (which aremostly lipophilic) to be dissolved in higher amounts than would bepossible in aqueous based solutions and effectively penetrate throughthe skin. Other solvents with this capacity can be found in theliterature. See, Holleran et. al., “Sphingolipids Are Required forMammalian Epidermal Barrier Function,” J. Clin. Investigation, Inc., 88,1338-1345 (1991), hereby incorporated by reference.

The solvent/water mixture is a mixture of water and at least one aproticsolvent. Typically, the aprotic organic solvent includes, but is notlimited to, an ester, aldehyde, or ketone. Typically, the organicsolvent has C₂-C₁₀ atoms. Preferably, the esters have C₂-C₆ atoms. Morepreferably, the ester is methyl formate, ethyl formate, propyl formate,methyl acetate, ethyl acetate, propyl acetate, methyl propionate, ethylpropionate, or propyl propionate. Most preferably, the ester is ethylacetate. Preferably, the aldehydes have C₂-C₄ atoms. More preferably,the aldehyde is acetaldehyde, propionaldehyde, or butyraldehyde. Mostpreferably, the aldehyde is propionaldehyde. Preferably, ketones haveC₃-C₆ atoms. More preferably, the ketone is acetone, butanone,pentanone, ethylisopropyl ketone, or rnethylisobutyl ketone. Mostpreferably, the ketone is acetone.

Typically, the aprotic organic solvent is present in an amount of 60% to90% by weight of the formulation. The water is present in an amount of2% to 20% by weight of the formulation.

The hair loss preventive ingredient should prevent hair loss, and mayalso promote hair growth. The hair loss preventive ingredients can be aninhibitor of DHT production and therefore an inhibitor of the mechanismunderlying hair loss. See Stamatiadis, et al. “Inhibition of 5alpha-reductase activity in human skin by zinc and azelaic acid,” Br. J.Dermatol. 119(5), 627-32 (1988), hereby incorporated by reference. Otheringredients may be known to promote hair growth. For example, seeBazzano et al., “Topical tretinoin for hair growth promotion,” J. Am.Acad. Dermatol., 15(4 Pt 2), 880-833 and 890-893 (1986). Typically, hairloss preventive ingredients include, but are not limited to, a C₆-C₁₄dicarboxylic acid, finasteride, minoxidil, tretinoin, or a herbalextract. Dicarboxylic acids are very soluble in the solvent/watermixture and once on the skin act as sebum absorbing particles whichfurther reduce the oiliness of the skin. Therefore, they may play adouble role in the formulation as a hair loss preventive ingredient andas a sebum reducing agent. Other dicarboxylic acids, such as azelaicacid, may act as an antibacterial agent which helps maintain asatisfactory hygiene level in the scalp and therefore preventsirritation and itchiness often associated with seborrhoea. See, Charnocket al., “Evaluation of the antibacterial efficacy of diesters of azelaicacid,” Eur. J. Pharm. Sci., 21(5), 589-96 (2004).

Preferably, the C₆-C₁₄ dicarboxylic acid is pimelic acid, suberic acid,azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, orbrassylic acid. Preferably, the herbal extract is saw palmetto extract.This extract is oil based and easily soluble in the composition.

The composition may further comprise at least one of antifungalcompound. Preferably, the antifungal compound include, but are notlimited to, zinc pyrithione, tar, selenium sulfide, ketoconazole, or teatree oil.

When the hair loss preventive ingredient is a dicarboxylic acid, it ispresent in an amount of about 2% to 30% by weight of the formulation andpreferably between 10% and 25% by weight. When the hair loss preventiveingredient is saw palmetto extract, it is present in an amount of about0.5% to 5% by weight of the formulation. When the hair loss preventiveingredient is finasteride, minoxidil, or tretinoin, it is present in anamount of about 0.001% to 5% by weight of the formulation. Additionally,when the antifungal compound is zinc pyrithione, it is present in anamount of about 0.001% to 5% by weight of the formulation.

These composition may contain one or more preservatives, coloringagents, anti-oxidants, water, acids, buffering agents, emulsifyingagents, thickeners, solvents, perfuming agents, and the like, andmixtures thereof.

Preservatives may include, but not limited to, tetrasodiumethylene-diamine tetraacetic acid (EDTA), methylparaben, benzophenone-4,methylchloroisothiazolinone, methylisothiazolinone, and the like, andmixtures thereof. Preservatives, when used, are typically present in anamount from about 0.01% to 6% by weight of the formulation, preferablyabout 0.05% to 4%, and more preferably from about 0.1% to 2% by weightof the formulation.

Coloring agents may include, but not limited to, FD&C Green No. 3, Ext.D&C Violet No. 2, FD&C Yellow No. 5, FD&C Red No. 40, and mixturesthereof. The coloring agents, when used, are typically present in anamount from about 0.001% to 0.1% by weight of the formulation, andpreferably from about 0.005% to 0.05% by weight of the formulation.

The formulation may further comprise anti-oxidants, both the enzymaticand non-enzymatic type. For example, superoxide dismutase (SOD),catalase, and glutathione peroxidase are natural enzymatic anti-oxidantsused by the body that may be supplemented with the compositions herein.Suitable non-enzymatic anti-oxidants may include, but not limited to,Vitamin E (e.g., tocopherol), Vitamin C (ascorbic acid), carotenoids,Echinacoside and caffeoyl derivatives, oligomeric proanthocyanidins orproanthanols (e.g., grape seed extract), silymarin (e.g., milk thistleextract, Silybum marianum), ginkgo biloba, green tea polyphenols, andmixtures thereof. Carotenoids are powerful anti-oxidants, and they mayinclude beta-carotene, canthaxanthin, zeaxanthin, lycopen, lutein,crocetin, capsanthin, and the like. Indeed, any pharmaceuticallyacceptable compounds suitable for administration orally or topically maybe used as an anti-oxidant in the compositions. The anti-oxidantcomponent, when used, is present in an amount sufficient to inhibit orreduce the effects of free-radicals at the scalp. The anti-oxidantcomponent may be present in an amount from about 0.001 to 1 weightpercent of the composition.

The invention encompasses a method of preventing hair loss comprisingapplying a hair loss prevention formulation in a therapeuticallysufficient amount to an area of skin and massaging the area of skinuntil the formulation is absorbed through the skin, wherein theformulation comprises a water/solvent mixture and at least one hair losspreventive ingredient known to inhibit the hormonal mechanism underlyingandrogenetic hair loss. The solvent is at least one aprotic organicsolvent and the hair loss preventive ingredient are those describedabove. The formulation may further comprise at least one antifungalcompound, such as those described above.

Having described the invention with reference to certain preferredembodiments, other embodiments will become apparent to one skilled inthe art from consideration of the specification. The invention isfurther defined by reference to the following example describing indetail the formation of the formulations for the hair loss prevention.It will be apparent to those skilled in the art that many modifications,both to materials and methods, may be practiced without departing fromthe scope of the invention.

EXAMPLES Example 1

The following ingredients were mixed using technology commonly availableto the skilled artisan to obtain the formulation described below.

Ingredient Amount (g) Percentage w/w Acetone 25.3 76% Water 1.7  5%Azelaic acid 6.7 20% Tretinoin 0.015 0.05%  

Example 2

The following ingredients were mixed using technology commonly availableto the skilled artisan to obtain the formulation described below.

Ingredient Amount (g) Percentage w/w Acetone 25.3 76% Water 1.7  5%Azelaic acid 5.9 17% Tretinoin 0.015 0.05%   Minoxidil 0.7  2%Finasteride 0.07 0.2% 

Example 3

The following ingredients were mixed using technology commonly availableto the skilled artisan to obtain the formulation described below.

Ingredient Amount (g) Percentage w/w Acetone 25.3 76% Water 1.7  5%Pimelic acid 3.3 10% Suberic acid 3.3 10% Saw Palmetto Extract 0.33  1%Zinc pyrithione 0.015 0.05%  

Example 4

The following ingredients (using other dicarbxylic acid with similarproperties) were mixed using technology commonly available to theskilled artisan to obtain the formulation described below.

Ingredient Amount (g) Percentage w/w Acetone 25.3 76% Water 1.7  5%Azelaic acid 5.9 17% Zinc pyrithione 0.015 0.05%   Minoxidil 0.7  2%Finasteride 0.07 0.2

Example 5

The following ingredients were mixed using technology commonly availableto the skilled artisan to obtain the formulation described below.

Ingredient Amount (g) Percentage w/w Acetone 25.3 76% Water 1.7 5%Azelaic acid 5.9 17% Ketoconazole 0.3 1% Minoxidil 0.7 2% Finasteride0.07 0.2

What is claimed is:
 1. A fomulation to treat hair loss comprising atleast one ingredient known to inhibit the hormonal mechanism underlyingandrogenetic hair loss, a C₆-C₁₄ dicarboxylic acid, and a mixture ofwater and at least one aprotic organic solvent, wherein the mixture ofwater and aprotic organic solvent is capable of solubilizing sebum andallowing the at least one ingredient to reach the skin and/or hairfollicle, and wherein the aprotic organic solvent is present in anamount of 60% to 90% by weight of the formulation and the water ispresent in an amount of 2% to 20% by weight of the formulation.
 2. Theformulation according to claim 1, wherein the aprotic organic solvent isselected from the group consisting of esters, aldehydes, ketones andmixtures thereof.
 3. The formulation according, to claim 2, wherein theketone is a C₂-C₆ ketone.
 4. The formulation according to claim 2,wherein the ester is methyl formate, ethyl formate, propyl formate,methyl acetate, ethyl acetate, propyl acetate, methyl propionate, ethylpropionate or propyl propionate.
 5. The formulation according to claim2, wherein the aldehyde is acetaldehyde, propionaldehyde orbutyraldehyde.
 6. The formulation according to claim 2, wherein theketone is acetone, butanone, pentarione, ethylisopropyl ketone, ormethylisobutyl ketone.
 7. The formulation according to claim 1, whereinthe dicarboxylic acid is pimelic acid, suberic acid, azelaic acid,sebacic acid, undecanedioic acid, dodecanedioic acid, or brassylic acid.8. The formulation according to claim 7, wherein the dicarboxylic acidis present in an amount of about 2% to 30% by weight of the formulation.9. The formulation according to claim 7, wherein the at east oneingredient is azelaic acid.
 10. The formulation according to claim 1,further comprising at least one antifungal compound.
 11. The formulationaccording to claim 10, wherein the antifungal compound is selected fromthe group consisting of zinc pyrithione, tar, selenium sulfide,ketoconazole, tree oil and combinations thereof.
 12. The formulationaccording to claim 1, wherein the formulation further comprisesminoxidil.
 13. A formulation to treat hair loss comprising: acetone in76% by weight of the formulation, water in 5% by weight of theformulation, azelaic acid in 17% by weight of the formulation, zincpyrithione in 0.05% by weight of the formulation, minoxidil in 2% byweight of the formulation, and finasteride in 0.2% by weight of theformulation, wherein the mixture of water and acetone is capable ofsolubilizing sebum and allowing the formulation to reach the skin and/orhair follicle.